基于FAERS数据库的多西环素不良事件信号挖掘与分析

Signal mining and analysis of adverse drug events of doxycycline based on FAERS database

目的利用美国食品药品管理局不良事件报告系统(FAERS)数据库挖掘多西环素导致的可疑不良事件(ADE)信号,为临床用药安全提供参考。方法提取FAERS数据库2004年第1季度至2024年第1季度的数据,经过数据清理和标准化处理,筛选出以多西环素为首要怀疑药物的ADE报告。利用《国际医学用语词典》对ADE报告进行系统/器官分类(SOC),并采用报告比值比法和综合标准法挖掘ADE信号,同时利用信息成分法判断信号强弱。结果共收集到以多西环素为首要怀疑药物的ADE报告共43126份,涉及患者14642例,女性患者构成比较高(57.32%)。共挖掘到ADE信号555个,累及SOC 26个,信号数排名前5位的SOC分别为胃肠系统疾病、皮肤及皮下组织类疾病、各类损伤、中毒及操作并发症、精神病类、感染及侵染类疾病。信号强度前5位ADE分别为赫氏反应、硬化性胆管炎、食管溃疡、胃肠黏膜坏死、胃肠道损伤。而说明书中未记载的信号强度前5位ADE信号为硬化性胆管炎、肾源性尿崩、肾小球肾炎微小病变、尿崩症、第Ⅵ颅神经性瘫痪。结论多西环素在临床应用中应高度重视其可能引发的频发及说明书未记载的ADE,这些ADE涉及肾脏及泌尿系统疾病、肝胆系统疾病、血管与淋巴管类疾病、内分泌系统疾病等多个SOC。临床药师应发挥关键作用,协助临床医生制定并实施ADE的预防方案,提高多西环素在临床使用的安全性。

Objective To mine adverse drug event(ADE)signals of doxycycline using the U.S.Food and Drug Administration Adverse Event Reporting System(FAERS)database,and provide scientific evidence for clinical medication safety.Methods The data from the FAERS database between the first quarter of 2004 and the first quarter of 2024 were extracted.After data cleaning and standardization,ADE reports with doxycycline as the main suspected drug were screened.The system organ class(SOC)of ADE was performed using MedDRA,and the reporting odds ratio method and Medicines and Healthcare products Regulatory Agency method were used to mine ADE signals.The information component method was also used to evaluate signal strength.Results A total of 43126 ADE reports with doxycycline as the primary suspected drug were collected,involving 14642 patients,with a higher proportion of female patients(57.32%).There were 555 related ADE signals involving 26 SOC,with the top 5 SOC being gastrointestinal disorders,skin and subcutaneous tissue disorders,injuries,poisonings,and procedural complications,psychiatric disorders,and infections and infestations.The top 5 ADE signals with the highest signal intensity were Hatch reaction,sclerosing cholangitis,esophageal ulcer,gastrointestinal mucosal necrosis,and gastrointestinal injury.Among the ADE signals with the strongest signal strength not listed in the package insert,the top five were sclerosing cholangitis,nephrogenic diabetes insipidus,minimal change glomerular nephritis,diabetes insipidus and Sixth cranial nerve paralysis.Conclusion In clinical practice,particular attention should be paid to the frequent ADEs caused by doxycycline,as well as those not yet documented in the package insert,which involve multiple SOC such as renal and urinary disorders,hepatobiliary diseases,blood and lymphatic system disorders,and endocrine disorders.Therefore,clinical pharmacists should play a key role in assisting clinicians to develop and implement prevention plans for ADEs,thereby improving the safety of doxycycline in clinical use.